Therapy for rheumatoid arthritis consists of a variety of specific treatments applied sequentially, either alone or in combination. Long- term management may thus be considered to be represented by a series of "therapeutic segments." This project analyzes the effectiveness, toxicity, and costs of each segment. It develops cost-effectiveness and toxicity-effectiveness ratios for each drug, conditional upon patient characteristics and prior therapy. The project introduces the important new clinical concepts of the "therapeutic segment" and of effectiveness conditioned upon immediately preceding therapy. The current project will evaluate new drug starts in over 7000 RA patients with many studied from the first year of disease. Effectiveness will be determined by drug effects upon disability levels, pain levels, and patient global assessments, determined by adjusted differences between pre- and post-treatment values over different time periods and at the beginning and end of therapeutic segments and by comparison of observed and expected values based upon linear regression in individual patients. Toxicity will be estimated by the Toxicity Index, with improved weighting techniques to be developed in the Project. Drug costs will be calculated as costs of drugs, costs of monitoring, costs of additional patient visits, and costs of treatment and prophylaxis for toxicity. This project builds upon large, long-term, high quality data sets, and techniques for estimation of effectiveness, toxicity, and costs developed by this team, in order to provide unique and important data to guide therapeutic choices toward improved outcomes for RA patients.